Anticancer treatment

It is my privilege to introduce this Handbook on Advanced Cancer Care,
which belongs to a series of publications initiated by the European Society
for Medical Oncology (ESMO). There is a great need, especially for medical
oncologists, to have a comprehensive overview of the essential elements
needed for the care of patients with advanced cancer. This handbook fulfills
these requirements.
The Handbook on Advanced Cancer Care provides useful definitions and
surveys of treatment principles.

With parallel breakthroughs occurring in molecular biology and nanoscience/technology, the newly
recognized research thrust on “nanomedicine” is expected to have a revolutionary impact on the
future of healthcare. To advance nanotechnology research for cancer prevention, diagnosis, and
treatment, the United States National Cancer Institute (NCI) established the Alliance for
Nanotechnology in Cancer in September 2004 and has pledged $144.3 million in the next five years
(for details, visit http://nano.cancer.gov).

Saporin is a type I ribosome-inactivating protein that is often appended
with a cell-binding domain to specifically target and kill cancer cells. Uroki-nase plasminogen activator (uPA)-saporin, for example, is an anticancer
toxin that consists of a chemical conjugate between the human uPA and
native saporin.

Previous studies have shown an anticancer effect of vitamin D, but the
mechanisms underlying this action have not been fully explored. Here we
show that 1,25-dihydroxyvitamin D3 (VD3, the active form of vitamin D)
significantly promoted apoptosis in the undifferentiated gastric cancer cell
line HGC-27, and this was accompanied by a concurrent increase in phos-phatase and tensin homolog deleted on chromosome 10 (PTEN) expression
on VD3 treatment.

Both microtubule destabilizer and stabilizer agents are important molecules
in anticancer therapy. In particular, paclitaxel has been demonstrated to be
effective for the treatment of ovarian, breast, and nonsmall cell lung carci-nomas. It has been shown that emergence of resistance against this agent
correlates with an increase in the relative abundance of tubulin isoform
bIII and that the more recently discovered IDN5390 can be effectively used
once resistance has emerged.

The spontaneous acquisition of resistance to a variety of
unrelated cytotoxic compounds has important implications
in medical treatment of infectious diseases and anticancer
therapy. In the yeast Saccharomyces cerevisiaethis pheno-menon is caused by overexpression of membrane efflux
pumps and is called pleiotropic drug resistance. We have
found that allelic forms of the genes for the transcription
activators Pdr1p and Pdr3p, designated PDR1-12and
PDR3-33,respectively, mediate resistance to diazaborine....

The mitochondrial transcription factor A (TFAM) is a member of a high-mobility group (HMG) family represented mostly by nuclear proteins.
Although nuclear localization of TFAM has been demonstrated in some
tumors and after treatment of tumor cells with anticancer drugs, the signifi-cance of these observations has not been fully elucidated.

The ultimate goal of cancer research is the development of effective anticancer
therapy. During the last several decades, the discovery of oncogenes, tumor
suppressors, growth factors, signal transduction pathways has dramatically
escalated our understanding of cancer cell biology and mechanisms of cell
transformation.1-3 Hundreds of cellular proteins and pathways have been logically
considered as molecular targets in a mechanism-based approaches of anticancer drug
development.4-6
Yet, the progress in cancer treatment has not paralleled these dramatic achievements
in basic research.